A yeast prion provides a mechanism for genetic variation and phenotypic diversity

A major enigma in evolutionary biology is that new forms or functions often require the concerted effects of several independent genetic changes. It is unclear how such changes might accumulate when they are likely to be deleterious individually and be lost by selective pressure. The Saccharomyces cerevisiae prion [PSI+] is an epigenetic modifier of the fidelity of translation termination, but its impact on yeast biology has been unclear. Here we show that [PSI+] provides the means to uncover hidden genetic variation and produce new heritable phenotypes. Moreover, in each of the seven genetic backgrounds tested, the constellation of phenotypes produced was unique. We propose that the epigenetic and metastable nature of [PSI+] inheritance allows yeast cells to exploit pre-existing genetic variation to thrive in fluctuating environments. Further, the capacity of [PSI+] to convert previously neutral genetic variation to a non-neutral state may facilitate the evolution of new traits.     

Repeated morphological evolution through cis-regulatory changes in a pleiotropic gene

The independent evolution of morphological similarities is widespread. For simple traits, such as overall body colour, repeated transitions by means of mutations in the same gene may be common. However, for more complex traits, the possible genetic paths may be more numerous; the molecular mechanisms underlying their independent origins and the extent to which they are constrained to follow certain genetic paths are largely unknown. Here we show that a male wing pigmentation pattern involved in courtship display has been gained and lost multiple times in a Drosophila clade. Each of the cases we have analysed (two gains and two losses) involved regulatory changes at the pleiotropic pigmentation gene yellow. Losses involved the parallel inactivation of the same cis-regulatory element (CRE), with changes at a few nucleotides sufficient to account for the functional divergence of one element between two sibling species. Surprisingly, two independent gains of wing spots resulted from the co-option of distinct ancestral CREs. These results demonstrate how the functional diversification of the modular CREs of pleiotropic genes contributes to evolutionary novelty and the independent evolution of morphological similarities.     

Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits

Phenotypic plasticity and the exposure of hidden genetic variation both affect the survival and evolution of new traits, but their contributing molecular mechanisms are largely unknown. A single factor, the yeast prion [PSI(+)], may exert a profound effect on both. [PSI(+)] is a conserved, protein-based genetic element that is formed by a change in the conformation and function of the translation termination factor Sup35p, and is transmitted from mother to progeny. Curing cells of [PSI(+)] alters their survival in different growth conditions and produces a spectrum of phenotypes in different genetic backgrounds. Here we show, by examining three plausible explanations for this phenotypic diversity, that all traits tested involved [PSI(+)]-mediated read-through of nonsense codons. Notably, the phenotypes analysed were genetically complex, and genetic re-assortment frequently converted [PSI(+)]-dependent phenotypes to stable traits that persisted in the absence of [PSI(+)]. Thus, [PSI(+)] provides a temporary survival advantage under diverse conditions, increasing the likelihood that new traits will become fixed by subsequent genetic change. As an epigenetic mechanism that globally affects the relationship between genotype and phenotype, [PSI(+)] expands the conceptual framework for phenotypic plasticity, provides a one-step mechanism for the acquisition of complex traits and affords a route to the genetic assimilation of initially transient epigenetic traits.     

Fitness reduction associated with the deletion of a satellite DNA array

Satellite DNA refers to a class of tandem repeats of very simple sequences, usually A + T or G + C rich, which form a satellite band on a CsCl gradient. Their ubiquity and abundance in higher eukaryotes have led to speculation about their functions. It has often been suggested that satellite DNAs are merely innocuous genetic parasites or comprise 'junk' DNA. The recent identification of an array of satellite DNA repeats as the Responder (Rsp) locus of Drosophila melanogaster provides a new perspective on these elements. Rsp is in the centromeric heterochromatin of most natural second chromosomes. It causes spermatids bearing it to degenerate after meiosis when the homologous second chromosome is a Segregation Distorter (SD) chromosome. That is, SD targets the Rsp locus on its homologue for destruction during spermatogenesis, causing meiotic drive. Why then does the Rsp locus, a large array of satellite repeats, exist at all? One plausible explanation is that its existence contributes to the fitness of flies bearing it, compensating for the loss through meiotic drive. A direct demonstration of the usefulness of any family of satellite DNA is to compare the fitnesses of individuals with and without it. Previously, such an experiment has been difficult because the absence of a characteristic phenotype has precluded an efficient selection of deletion mutations. In this report we attempt to demonstrate a fitness reduction associated with the deletion of Rsp satellite DNA as well as the life stages at which such a reduction occurs.